A variety of localized delivery methods are available, such as convection enhanced delivery (CED) which provides for the distribution of nucleic acids in a homogeneous, targeted fashion to solid tissues in clinically useful volumes. However, the binding of a nucleic acid to binding sites other than the intended target of the nucleic acid limits the volume of distribution (Vd).
To overcome this limitation, the present invention provides methods of increasing the volume of distribution of a nucleic acid during various modes of delivery, such as, for example, CED, comprising administering a nucleic acid and a facilitating agent to, for example, a tissue or a subject, whereby the inclusion of the facilitating agent increases the volume of distribution of the nucleic acid. These methods can be utilized to treat a variety of disorders, such as neurodegenerative disorders and cancer.